July 3, 2013
Triple Therapy Lowers New Diabetics’ A1c, Weight, Hypoglycemia Risk

Chicago—A multistep process of initiating metformin and then adding a sulfonylurea (glyburide) and, eventually, basal insulin glargine is the usual recommendation for patients newly diagnosed with type 2 diabetes.

A new study suggests, however, that starting those patients on triple therapy of metformin, pioglitazone, and the glucagon-like peptide-1 (GLP-1) agonist exenatide, marketed as Byetta by AstraZeneca/Bristol-Myers Squibb, has significant benefits over typical treatment in reducing HbA1c, hypoglycemia, and weight gain.

The study, lead by Muhammad A. Abdul-Ghani, MD, PhD, of the University of Texas Health Science Center at San Antonio, was presented at the American Diabetes Association (ADA) 2013 Scientific Sessions in Chicago.

According to the study background, “step-wise addition of metformin sulfonylurea and basal insulin reduced microvascular complications, but A1c rose progressively to [greater than] 8.5% and [about] 65% of individuals required insulin therapy after 10.5 years.” Researchers sought to determine the efficacy and safety of initiating therapy in new-onset diabetes patients with the triple therapy approach instead of metformin followed by sequential addition of sulfonylurea and basal insulin, a treat-to-fail approach.

The study involved 147 type 2 diabetes patients, diagnosed within the last 6 months, and with an average age of 45, BMI around 36, and A1c about 8.6. Of the study group, 71 were randomized to receive the so-called triple therapy, an initial combination of metformin (1,000-2,000 mg/d) plus pioglitazone (15-45 mg/d) plus exenatide (5-10 mcg BID). At the same time, 76 received conventional therapy, an escalating dose of metformin (1,000-2,000 mg/d) followed by sequential addition of glipizide (5-20 mg/d) and then basal insulin to maintain A1c < 6.5%.

“In subjects receiving triple therapy, A1c decreased from 8.6 to 6.1% at six months and remained stable at 6.1% at 24 months,” according to the authors. “With conventional therapy, A1c declined to 6.1% at six months and then increased to 6.6% at 24 months.”

In addition, more patients in the conventional therapy group failed to achieve the treatment A1c goal of under 6.5% (46% vs. 22% P < 0.0001). The authors also noted that, despite significantly lower A1c, subjects in the triple-therapy group experienced a 13.6-fold lower rate of hypoglycemia compared to patients in the other group. They also had mean weight loss of 1.2 kg versus 3.6 kg weight gain (P = 0.02) in subjects on conventional therapy.

“Antidiabetic therapy targeting the core metabolic defects (insulin resistance and beta cell dysfunction) responsible for hyperglycemia is more effective and safer than therapy simply aimed at lowering [plasma glucose] without correcting the underlying pathophysiologic disturbances present…,” the authors conclude.

U.S. Pharmacist Social Connect